1. Field of the Invention
The present invention relates to novel microorganisms belonging to the Bacillus subtilis subspecies and a novel antifungal complex produced therefrom, which has a variety of useful applications such as a low toxicity agricultural fungicide, a therapeutic agent against fungal infections, a food preservative, a skin moisturizing agent and the like. The present invention also relates to processes for producing said complex from said microorganisms.
2. Description of the Prior Art
Antifungal agents are generally divided into two groups: those which are derived from microbial organisms and those which are chemically synthesized. In the former category, for instance, in 1939, Oxford et al. isolated griseofulvin from the culture of Penicillium griseofulvum[see Oxford, A. E., Raistrick, H. and Simonart, P., Biochem. J., 33:240(1939)], which was initially developed as a pesticide and then further developed to be used as an effective oral preparation for the treatment of dermatophytosis; in 1950, nystatin was separated from Actinomycetes by Hazen, et al. [see Hazen, E. L. and Brown, R., Science, 112:423(1950)]; and, in 1955, amphotericin B was isolated from Actinomycetes by Gold, et al.[see Gold, W., Stout, H. A., Pagano, J. F. and Donovick, R., Antibiot. Ann., 1956:579(1955)]. As for the latter category, such comunds as 5-flurocytosines and ketoconazoles were recently developed.
While the chemotherapy for bacterial infections made a great deal of progress, similar results were not achieved in the case of treating fungal infections. Accordingly, development efforts for antifungal agents active against a broad spectrum of fungi including Candida and Aspergillus with little side-effects continued.
As a result, in the early 1960's, various agricultural fungicides were developed; and relatively high toxic pesticidal compounds were replaced with new antifungal agents such as: blasticidin S and kasugamycin for controlling leaf blast of rice[see Takeuchi, S., Hirayama, K., Ueda, K., Sakai, H. and Yonehara, H., J. Antibiotics, 11A:1-5(1958); and Umezawa, H., Okami, Y., Hishimoto, T. Suhara, Y., Hamada, M. and Takeuchi, T., J. Antibiotics, 18:101-108(1965)]; polyoxin and validamycin, both effective against sheath blight[see Isono, K., Nagatsu, J., Kawahima, Y. and Suzuki, S., Agric. Biol. Chem. 29:848-854(1965); and Iwasa, T., Yamamoto, H. and Shibata, M., J. Antibiotics, 23:595-602(1970)]; and mildiomycin useful in controlling barley's powdery mildew[see Harada, S. and Kishi, T., J. Antibiotics, 31:519-524(1978)].
Despite these limited successes, however, needs have continued to exist for the discovery of non-toxic antifungal agents having a broad spectrum of activity.